Ethos Technologies Inc.

Good afternoon, ladies and gentlemen, and welcome to the Atire Pharma fourth quarter and full year 2024 conference call. At this time, all participants are in a listen only mode. Later, we will conduct a question and answer session and instructions will be given at that time. As a reminder, this conference is being recorded for replay purposes. It is now my pleasure to hand the conference call over to Ashley Dunston, a TIRES Senior Director of Investor Relations and Public Affairs. Ms. Dunstan, you may begin.

Thank you and good afternoon, everyone. Thank you for joining us today to discuss a TIRES fourth quarter and full year 2024 operating results and corporate update. We are joined today by Dr. Sanjay Shukla, our President and CEO, Ms. Jill Broadfoot, our CFO, and Dr. Leslie Nangle, Vice President of Research. On the call, Sanjay will provide an update on our corporate strategy, including our clinical program for efsofitamide. Leslie will discuss our research and discovery programs while Jill will review the financial results and our current financial position before handing it back to Sanjay to open up the call for any questions. Before we begin, I want to remind everyone that except for statements of historical facts, the statements made by management and responses to questions on this conference call are forward-looking statements under the safe harbor provision of the Private Securities Litigation Reform Act of 1995. These statements involve risks and uncertainties that can cause actual results to differ materially from those in such forward-looking statements. Please see the forward-looking statement disclaimer in the company's press release issued this afternoon, as well as the risk factors in the company's SEC filings and included in our most recent annual report on Form 10-K, subsequently filed quarterly reports on Form 10-Q, and in our other SEC filings. Undue reliance should not be placed on our forward-looking statements, which speak only as of the date they are made, as facts and circumstances underlying those forward-looking statements may change. Except as required by law, Atire Pharma disclaims any obligation to update these forward-looking statements to reflect future information, events, or circumstances. I will now turn the call over to Sanjay.

Thank you, Ashley. Good afternoon, everyone, and thank you for joining us for our fourth quarter and full year 2024 results conference call. At Atire, we're on a mission to translate tRNA synthetase biology into new therapies for fibrosis and inflammation. Our lead therapeutic candidate, efsofitimod, is a first-in-class biologic immunomodulator that selectively modulates activated myeloid cells via Neuropilin 2. or NRP2 to resolve inflammation without immune suppression and potentially prevent fibrosis progression. We're developing efsofitamide as a treatment for patients with interstitial lung disease or ILD, a group of rare immune mediated disorders that can cause chronic inflammation and fibrosis of the lungs. 2024 was an important year for ATAR as we completed enrollment in our Global Pivotal Phase III Epsophit Study of Epsophitamide in patients with pulmonary sarcoidosis, a major form of ILD that is our lead indication. This is the largest interventional study ever conducted in pulmonary sarcoidosis, and we look forward to releasing top-line data from this study in the third quarter of this year. Epsophit is a randomized, double-blind, placebo-controlled 52-week study It consists of three parallel cohorts randomized equally to either three milligrams per kilogram or five milligrams of kilogram of esophitamide or placebo. Dosed intravenously monthly for a total of 12 doses. The study enrolled 268 patients at 85 centers in nine countries. The trial design incorporates a forced steroid taper with steroid reduction as the primary endpoint of the study. Secondary endpoints include measures of sarcoidosis quality of life and lung function. Patients who complete the study and wish to receive treatment with efsofitimab outside of the clinical trial are eligible to participate in an individual patient expanded access program, or EAP. The EAP was implemented primarily based on feedback from multiple study principal investigators, or PIs, whose patients requested to continue treatment once they completed the study. These patients will receive five milligrams per kilogram of efsofitamide while in the EAP. However, PIs, patients, and the company remain blinded to the efsofit treatment assignments of these EAP patients. Additionally, we have now held four positive data and safety monitoring report or DSMB reviews for this study, all of which have identified no safety concerns and recommended that the study continue unmodified. The most recent pre-planned independent review indicates that the study continues to track well from a safety standpoint. We remain confident in the favorable safety profile we have seen for esophidema to date, which we believe is a key value proposition of the drug. And finally, We'll get our first look at the blinded baseline demographic and disease characteristics of the patients enrolled in the study at the upcoming American Thoracic Society Conference, or ATS, which is scheduled to take place mid-May in San Francisco. In a poster, we will be able to get a sense for the profile of the patients enrolled, including baseline steroid dose and background immunomodulator use. and how the profile matches the inclusion and exclusion criteria for the study. As part of our planning for the phase three readout for SOFIT, we recently held a type C meeting with the US Food and Drug Administration or FDA. The main objective of this meeting was to discuss the statistical analysis plan or SAP for the study, including how the primary and secondary endpoints are assessed statistically. For the primary endpoint, we determined how steroid reduction will be analyzed in the SAP. As we previously discussed, we initially proposed that we measure steroid reduction based on calculating the average daily steroid dose between week 12 and week 48, which is the protocol-specified post-steroid taper period. We viewed this as a conservative way of measuring steroid reduction in the study. Based on FDA feedback, We will now measure steroid reduction as the absolute change from baseline to week 48. We feel this change creates a more simplified assessment to capture potential steroid delta between groups. The statistical powering for the study remains intact, and we are pleased with the clarification around how we will measure steroid reduction. With limited clinical studies in sarcoidosis as a benchmark, We are pioneering a path forward to measure how we can potentially improve the lives of these patients. While we brought you up to date on FSOFIT, I want to take a few minutes to provide you with critical insights into the pulmonary sarcoidosis landscape in the U.S. that have emerged from some of our early pre-commercial activities. We believe these findings support a potentially larger market opportunity for FSOFITimod and sarcoidosis. Pulmonary sarcoidosis is a disease characterized by the formation of granulomas, or clumps of immune cells, predominantly in the lungs. The current standard of care is oral corticosteroids, which may help improve symptoms in the short term, but come with serious side effects with long-term use. And despite the use of steroids and other off-label immunosuppressive agents, many patients have disease that progresses, with around 20% developing lung fibrosis, which can lead to organ failure and death. There remains a lack of safe and effective treatments available for these patients. It is typically reported that sarcoidosis affects close to 200,000 people in the US, with 90% of patients having lung involvement. A third-party claims analysis, which we conducted late last year, confirms that number and shows that the number of patients diagnosed with lung involvement similar to the population enrolled in our phase three trial is 30% higher than previously estimated. Since the US epidemiology numbers most frequently referenced were published nearly a decade ago, we were not surprised that the population has grown. Furthermore, when we looked at treatment practices, such as the number of patients that require any treatment and those that are prescribed steroids, we saw that nearly 75% of diagnosed patients are prescribed steroids, which is well above previous estimates in the US and at the upper range as to what is reported globally. Furthermore, the claims also showed significant mortality and hospitalization rates, which speak to the high unmet medical need for this disease. When it comes to pricing, Through additional payer research that we conducted, we continue to see positive feedback from payers regarding their willingness to reimburse for an on-label biologic in sarcoidosis. We are encouraged by the reimbursement landscape we've seen recently, where some rare disease product launches have included steroid reduction as part of the label and are priced at a premium. In sum, we believe the findings from these recent activities support the patients' and physicians' need and strong desire for a product like efsofitamide. We view efsofitamide as a potential frontline steroid-reducing agent in patients with moderate to severe disease, which could address 50 to 75% of all sarcoidosis patients. We've previously stated that we estimate a total global market opportunity for efsofitamide in ILD at $2 to $5 billion. And our updated research supports a market where sarcoidosis represents a significant portion of that range. Some of these insights that we've discussed will be presented in two posters at ATS in May. And this work has enhanced our understanding of the sarcoidosis market in the U.S., in a way that will be foundational for preparing for some of our upcoming commercial readiness activities. Finally, as we start to plan for commercial readiness, we recently appointed Eric Benevich, who is currently the Chief Commercial Officer for Nurocrine Biosciences to our board of directors. Eric brings a wealth of experience in launching high value pharmaceuticals, including most recently a product for a rare disease that has a steroid reduction component as part of its Phase III clinical trial and FDA approval package. We anticipate his contributions will be highly valuable as we advance efsofitamod to a commercial product. Now let's turn to our second indication for efsofitamod, ILD-related systemic sclerosis or SSC, which is also known as scleroderma. SSC is a form of connective tissue disease where ILD commonly occurs and is a leading cause of mortality. Current treatment options for SSC ILD are limited, and like sarcoidosis, they do not treat the underlying disease or improve quality of life. EpsilConnect is a Phase II randomized, double-blind, placebo-controlled, proof-of-concept, 28-week study to evaluate two fixed doses of Epsilfitamide. 270 milligrams or 450 milligrams, compared to placebo. Patients are dosed intravenously monthly for a total of six doses. This study is currently enrolling patients with limited and diffuse SSC-ILD at multiple centers in the U.S. The primary endpoint of the study is lung function as measured by forced vital capacity, and key secondary endpoints include symptom control and skin assessments. We expect to release interim data from the study in the second quarter of this year. The interim data will focus on skin assessments measured at baseline in week 12 for approximately eight patients, including patients on drug and placebo. We plan to present findings for skin histopathology, including immune biomarkers and the modified Rodman skin score, which will provide insight regarding potential changes in skin tissue. Skin manifestations in SSC highly impact the quality of life for these patients, and other therapies showing improvement in these measures have had limited to no success. This interim data may provide us with an early signal related to skin changes and may help inform the clinical development strategy for this indication. Because we plan to evaluate skin assessments in the interim data, do not plan to include any data related to lung function, we see limited read-through from this data to the Phase III top-line data in pulmonary sarcoidosis that we will present later this year. I will now turn the call over to Leslie Nangle, our Vice President of Research, to discuss our research and discovery programs.